Highly pathogenic avian influenza (HPAI) subtype H5N1 persists in a number of countries in Asia and Africa, and continues to evolve in wild birds, domestic poultry and humans. Recent laboratory results have shown that re-assortment between HPAI H5N1 and human H3N2 influenza virus may result in a hybrid virus with substantial virulence. The spillover of avian influenza at the human-animal interface is a major public health concern. The long-term goal of this proposed study is to improve our capability to predict the dynamics and spillover risk of avian influenza at the human - animal interface and to improve risk-based influenza surveillance, preparedness, responses, intervention, and public health policy making. Rapidly changing agricultural intensification, landscapes and markets over the past few decades have resulted in significant changes in the size and spatial distribution of poultry and pig farms as well as their connectivity between farms, which affect the dynamics and spillover of avian influenza at the human- animal interface. This proposed project is centered on three specific aims: (1) to quantify avian influenza transmission dynamics between multiple poultry farms accounting for different farm sizes, management practices and different structures of network connectivity; (2) to quantify the spillover risk of avian influenzaat the human - poultry - wild bird interface, and evaluate occupational exposure risk of workers in poultry and pig farms; and (3) to assess the effectiveness of various scenarios and intervention measures for disease control and management. This project will use advanced geospatial technology to collect data relevant to poultry farms, poultry and wild bird movement, and connectivity between farms in Poyang Lake, China and Thailand. It will also conduct questionnaire surveys and serum samples of people who work on poultry and pig farms. Finally, a suite of mathematical, statistical and agent-based models will be developed and used to assess the effectiveness of various scenarios and intervention measures on avian influenza transmission and spread. Whilst this proposal is focused on HPAI H5N1, the results and methodology would apply to other influenza viruses, and some of the outputs and modeling approaches will also be relevant to other diseases emerging in response to fast change in the agricultural sector and landscapes. The project will further strengthen the international collaboration amongst the USA, China, Thailand, UK and Belgium in the area of disease ecology and public health, which will make a significant contribution to the mission of the NIH and NIAID.